This project was initiated to evaluate the relationship between chemically induced mutagenesis and carcinogenesis. The primary emphasis is placed on antitumor agents, known environmental contaminants and model chemical carcinogens. A sensitive in vitro microbial test system is used for the detection of chemical mutagens. The research is directed at present to determine: (1) the role, if any, and the mechanism of metabolic activation in the mutagenesis caused by antitumor agents and chemical carcinogens; (2) the predictive value of the in vitro mutagenesis test for in vivo carcinogenesis; (3) the difference if any, between the mutagenic effects of antitumor agents and other chemical mutagens in mammalian and microbia cell syytems; (4) the effect of structural modification on the mutagenicity of antitumor agents and model chemical carcinogens; (5) the relationship between the in vivo and in vitro protective effects of nucleophiles, such as L-cysteine, N-acetyl-cysteine and cysteamine, against toxicity of antitumor agents.